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Characterizing single cell states of activated and transformed B cells in rhesus macaque models

Award Number: R21AI171354
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Epstein-Barr virus (EBV) causes significant disease in patients with congenital or acquired immune deficiencies. Elucidating markers of early cancer and understanding tumor composition are essential in improving diagnostics and therapies for EBV diseases. In vitro, EBV infection of B cells induces formation of lymphoblastoid cell lines (LCLs) which mimic properties of lymphoproliferative disease and serve as a model to investigate B cell transformation processes. Multiple viral gene products dramatically reprogram the B cell environment, and several host factors critical for maintaining LCL proliferation have been identified; however, host factors leading to LCL outgrowth as well as the distinct cellular substages required for establishment of persistent infection and B cell transformation are less understood. Deciphering the molecular mechanisms involved in these processes is an ongoing challenge due to the refractory nature of primary B cells for genetic manipulation and the observed heterogeneity in viral and cellular gene expression detected through standard bulk transcriptome analysis. To address gaps in our current knowledge, we will use multi-omic single-cell approaches to define B cell molecular signatures and cell markers that delineate early virus-mediated transformation. For these studies, we will investigate a pre-clinical EBV model, rhesus macaque (RM) cells and tumor tissues infected with rhesus lymphocryptovirus (rLCV). By simultaneously measuring immunophenotypes and gene expression, we aim to identify B cell states that successfully navigate infection towards the LCL trajectory. Leveraging these approaches to further analyze rLCV+ lymphoid tissues, we aim to define biological properties of pre-cancerous and cancerous states at the single cell level.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $177,909 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	2	2/22/2024	NON-COMPETING CONTINUATION	$177,909
														Subtotal = $177,909

Issue Date FY: 2023 ( Subtotal = $236,176 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	1	3/2/2023	NEW	$236,176
														Subtotal = $236,176

Grand Total All Awards = $414,085

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Characterizing single cell states of activated and transformed B cells in rhesus macaque models

Award Number: R21AI171354

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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